-- Registrational data in RET fusion-positive NSCLC show 61% ORR in patients previously treated with platinum-based chemotherapy and 73% ORR in treatment-naïve patients –

-- 12% complete response rate in patients with treatment-naïve RET fusion-positive NSCLC –

-- Median DOR not reached across lines of therapy in RET fusion-positive NSCLC, with 6-month DOR of 86% --

-- NDA accepted by FDA and MAA validated by EMA for pralsetinib in RET fusion-positive NSCLC –

Suzhou, China, May. 30, 2020 -- The partner of CStone Pharmaceuticals (“CStone”, HKEX: 2616), Blueprint Medicines, announced data from the ongoing ARROW clinical trial of pralsetinib in patients with RET fusion-positive non-small cell lung cancer (NSCLC), thyroid cancer and other solid tumors. Registrational data for pralsetinib in patients with RET fusion-positive NSCLC showed deep and durable clinical responses, with a median duration of response (DOR) not reached. Additional results showed the broad clinical activity of pralsetinib across other RET fusion-positive tumors, including thyroid cancer. Pralsetinib was well-tolerated and safety results were consistent with prior data, with no new safety signals observed. These results are being presented during the American Society of Clinical Oncology 2020 (ASCO20) Virtual Scientific Program.

In addition, Blueprint Medicines announced that the U.S. and EU marketing applications for pralsetinib for the treatment of locally advanced or metastatic RET fusion-positive NSCLC have been accepted by the U.S. Food and Drug Administration (FDA) and validated by the European Medicines Agency (EMA), respectively. The FDA granted priority review and set an action date of November 23, 2020 under the Prescription Drug User Fee Act. Blueprint Medicines plans to submit an NDA for pralsetinib for advanced RET mutant and RET fusion-positive thyroid cancers in June 2020, under the FDA’s Oncology Center of Excellence Real-Time Oncology Review pilot program.

Clinical Activity Data

The reported data included response-evaluable populations comprising 116 patients with NSCLC who received a starting dose of 400 mg once daily (QD), including 80 patients with NSCLC previously treated with platinum-based chemotherapy and 26 patients with treatment-naïve NSCLC, 11 patients with RET fusion-positive thyroid cancer, and 12 patients with other RET fusion-positive cancers. Tumor response was assessed by blinded, independent central review using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

RET Fusion-Positive NSCLC

As of a data cutoff of November 18, 2019, pralsetinib demonstrated consistent and robust clinical activity in RET fusion-positive NSCLC, regardless of prior therapy, RET fusion partner or central nervous system (CNS) involvement.

In 80 patients who previously received platinum-based chemotherapy, the ORR was 61 percent (95% CI: 50-72%). Two partial responses (PR) were pending confirmation at the time of the data cut off and were subsequently confirmed. Five percent of patients had a confirmed response (CR) and 14 percent of patients had complete regression of target tumors.

In 26 patients with no prior systemic therapy, the confirmed ORR was 73 percent (95% CI: 52-88%), and the CR rate was 12 percent.

Across all 116 patients, regardless of prior therapy, the median DOR was not reached (95% CI: 11 months, not reached), and the 6-month DOR was 86 percent. Overall, 74 percent of confirmed responders, including all patients with CRs, were on treatment as of the data cutoff.

Robust and durable intracranial activity was shown in nine patients with measurable CNS metastases at baseline. All patients had shrinkage of CNS metastases, with an intracranial CR rate of 33 percent. No CNS responders experienced CNS progressive events. The median CNS DOR was not reached, with ongoing treatment durations up to 12 months in patients with measurable CNS metastases. Among patients without a history of CNS metastases, none have developed new CNS metastases on study as of the data cutoff date.

Other RET Fusion-Positive Cancers

As of a data cutoff of February 13, 2020, pralsetinib demonstrated robust clinical activity in a range of additional RET fusion-positive cancers. In 11 patients with RET fusion-positive thyroid cancer (10 previously treated with systemic therapy), the centrally confirmed ORR was 91 percent (95% CI: 59-100%), and the disease control rate was 100 percent (95% CI: 72-100%). Overall, 70 percent of responders remain on therapy with ongoing treatment durations up to 22 months as of the data cutoff. Across 12 patients with other RET fusion-positive cancers previously treated with systemic therapy, the investigator-assessed ORR was 50 percent (95% CI: 21‒79), with one PR pending confirmation. Responses were observed in all evaluable patients with pancreatic adenocarcinoma (n=3) and cholangiocarcinoma (n=2), tumor types with a typically poor prognosis.

Safety Data

As previously reported, as of the data cutoff date of November 18, 2019, a total of 354 patients were enrolled in the ARROW trial at a starting dose of 400 mg QD. Overall, safety results were consistent with previously reported data. Pralsetinib was well-tolerated across tumor types, and most treatment-related adverse events (AEs) were Grade 1 or 2.

The most common treatment-related AEs reported by investigators (≥15 percent) were increased aspartate aminotransferase (AST), anemia, increased alanine aminotransferase (ALT), constipation, hypertension and neutropenia. Investigator-reported Grade 3 or higher treatment-related AEs (≥5 percent) were hypertension, neutropenia and anemia. Only 4 percent of patients discontinued pralsetinib due to treatment-related AEs.

#

About Pralsetinib

Pralsetinib is an investigational, once-daily oral precision therapy specifically designed for highly potent and selective targeting of oncogenic RET alterations. Blueprint Medicines is developing pralsetinib for the treatment of patients with RET-altered NSCLC, thyroid cancer and other solid tumors. The FDA has granted Breakthrough Therapy Designation to pralsetinib for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy, and RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

Pralsetinib was designed by Blueprint Medicines’ research team, leveraging the company’s proprietary compound library. In preclinical studies, pralsetinib consistently demonstrated sub-nanomolar potency against the most common RET fusions, activating mutations and predicted resistance mutations. In addition, pralsetinib demonstrated markedly improved selectivity for RET compared to pharmacologically relevant kinases, including approximately 80-fold improved potency for RET versus VEGFR2. By suppressing primary and secondary mutants, pralsetinib has the potential to overcome and prevent the emergence of clinical resistance. Blueprint Medicines believes this approach will enable durable clinical responses across a diverse range of RET alterations, with a favorable safety profile.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of pralsetinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for pralsetinib in the rest of the world.

About Cstone

CStone Pharmaceuticals (HKEX: 2616) is a biopharmaceutical company focused on developing and commercializing innovative immuno-oncology and precision medicines to address the unmet medical needs of cancer patients in China and worldwide. Established in 2015, CStone has assembled a world-class management team with extensive experience in innovative drug development, clinical research, and commercialization. The company has built an oncology-focused pipeline of 15 drug candidates with a strategic emphasis on immuno-oncology combination therapies. Currently, 5 late-stage candidates are at pivotal trials. With an experienced team, a rich pipeline, a robust clinical development-driven business model and substantial funding, CStone’s vision is to become globally recognized as a leading Chinese biopharmaceutical company by bringing innovative oncology therapies to cancer patients worldwide.

For more information about CStone Pharmaceuticals, please visit:

Forward-looking Statement

The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.